Adenovirus Nephritis: A Pathologic Perspective

In a recent article published in the American Journal of Kidney Diseases, Keddis et al present a very instructive case of adenoviral infection in an umbilical cord blood transplant recipient. The patient presented with acute kidney injury in the setting of hemorrhagic cystitis. A kidney biopsy showed a granulomatous interstitial nephritis, and a diagnosis of adenovirus infection was made by polymerase chain reaction (PCR) for viral DNA in the plasma and in-situ hybridization on the biopsy material.

While the case is a textbook example of adenovirus nephritis, a wider spectrum of pathology is described in the literature and needs to be kept in mind by physicians caring for immunocompromised patients. Adenovirus infection can also present as asymptomatic viremia, acute tubular necrosis, pyelonephritis, ureteric stricture, and mass lesions in the kidney. In some cases, kidney biopsy shows only a banal interstitial nephritis with no viral inclusions, presumably because of the focal nature of viral infection in the kidney. Diagnosis in such cases can be clinched by urine examination showing white cell casts and decoy cells, and PCR on the urine testing positive for viral DNA. In medical centers with good electron microscopy facilities, scanning electron microscopy on the urine sediment can show viral capsids measuring approximately 70 nm in diameter. When clinical suspicion is high, multiple diagnostic modalities may be necessary to clinch the diagnosis. Some PCR primers and antibodies used for immunohistochemistry may not provide complete coverage against all 51 serotypes of adenovirus. A culture for adenovirus usually becomes positive in 2-7 days, but group D strains may not grow for up to 4 weeks, while group F strains (serotypes 40 and 41) do not grow at all and may require ELISA (enzyme-linked immunosorbent assay) testing for diagnosis. Adenovirus nephritis has been now described in cases following kidney transplantation and stem cell transplantation. A high index of suspicion is needed to diagnosis this entity.

It is also worth noting that the creatinine in the patient reported did not return to normal after PCR for adenovirus showed disease resolution of infection. This illustrates the impact of multiple nephrotoxic insults in hematopoietic stem cell transplant recipients. Potential causes of acute kidney injury in this patient population include hypotension, sepsis, medications, thrombotic microangiopathy, and conditioning regimens that utilize radiation as well as chemotherapy.

Parmjeet Randhawa, MD
Professor of Pathology, University of Pittsburgh Medical Center
AJKD Associate Editor

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